Menthol for PDT Pain Relief (MentholPDT)

A Randomised Double Blind, Placebo Controlled Study of the Efficacy of Topical Menthol for Pain Relief During Topical Photodynamic Therapy

Topical photodynamic therapy (PDT) is widely used to treat superficial non-melanoma skin cancer (NMSC) and dysplasia, notably actinic keratosis and may also be effective in a range of other dermatological conditions. A major limitation of PDT is pain during irradiation. A lack of knowledge of the mechanism of PDT-induced pain has limited the development of effective approaches for prevention or relief of this adverse effect. The investigators have investigated the possible efficacy of menthol for PDT pain ex vivo and will now study this in a clinical trial. This proposal describes the prospective randomised double blind, placebo controlled clinical trial that will be undertaken to investigate the use of topical menthol for PDT-induced pain relief in patients with actinic keratosis of the face and scalp who will be attending general dermatology and PDT outpatient clinics at Ninewells Hospital, Dundee.

Study Overview

• Status: Completed
• Conditions: Actinic Keratosis
• Intervention / Treatment: Drug: Menthol; Drug: Aqueous Cream

Detailed Description

This proposal describes the prospective randomised double blind, placebo controlled clinical trial that will be undertaken to investigate the use of topical menthol for PDT-induced pain relief in patients with actinic keratosis of the face and scalp who will be attending general dermatology and PDT outpatient clinics at Ninewells Hospital, Dundee.

This will be undertaken by comparison of 5% menthol in aqueous cream with aqueous cream as placebo and the primary outcome measures will be pain recorded on a visual analogue scale (VAS) during and up to 24 h after PDT. Secondary outcomes are phototoxicity, assessed by a semi-quantitative scoring system immediately after PDT, fluorescence assessed routinely after cream application and before irradiation and outcome based on clinical assessment three months after PDT and patient evaluation. Patients will be involved in the study from the first visit for PDT until the three-month assessment visit after PDT. Data analysis will be undertaken using within-subject paired analyses as patients act as their own control. Information from this study will inform investigators as to whether topical menthol should be routinely incorporated into PDT treatment regimens in order to reduce pain and increase tolerance of treatment. The information will also provide additional information as to the mechanisms of PDT-induced pain and its possible prevention and/or relief.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • Dundee, United Kingdom, DD1 9SY
    • Ninewells Hospital and Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

A subject will be eligible for inclusion in this study only if all of the following criteria apply:

1. Adults >18 years. Target population is men or women ≥50 years (only post-menopausal women)
2. Presence of actinic keratoses (AK) on the face and scalp involving both right and left comparable sites.
3. Free of significant physical abnormalities (e.g. tattoos, dermatoses) in the potential treatment area that may cause difficulty with examination or final evaluation.
4. Able to understand and adhere to protocol requirements.

Exclusion Criteria:

1. Unable to give written informed consent.
2. Allergy to menthol, aqueous cream or excipients
3. Participation in a drug trial or other interventional study within 30 days of recruitment to this study
4. Pre-menopausal women, pregnancy, breast feeding, planning to conceive
5. Chronic pain

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Menthol; 5% menthol in aqueous cream (Dermacool Forte)	Drug: Menthol; Topical menthol in aqueous cream; Other Names: 5% menthol in aqueous cream
PLACEBO_COMPARATOR: Placebo; Aqueous cream	Drug: Aqueous Cream; placebo; Other Names: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain immediately after PDT assessed by VAS score	pain immediately after and at 3, 6 and 24 h after PDT assessed by VAS score	24h

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clearance: clear/partially clear/not clear - clinical assessment visually and by palpation	Clearance (CR), partial clearance (PR) or no clearance (NR) will be recorded on each side in each participant	3 months after treatment
Erythema (redness) (none/mild/moderate/severe)	Erythema grading (none/mild/moderate/severe) will be recorded on each side in each participant	Immediately after PDT
fluorescence assessed as none/mild/moderate/strong using Wood's light examination	Fluorescence of each side in each participant will be recorded	Immediately before and after PDT
patient preference - preferred right or left side or no preference	patient questionnaire completed at home and returned in SAE	24h
swelling	Swelling present or absent will be recorded on each side in each patient	immediately after PDT
Exudation	Exudation present or absent will be recorded on each side in each patient	immediately after PDT
urticaria	Urticaria present or absent will be recorded on each side in each patient	immediately after PDT

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blinding - patient will be asked which side they think the menthol was used on or if they do not know	patient questionnaire completed at home and returned in SAE	24h

Collaborators and Investigators

• Sponsor: University of Dundee
• Investigators: Principal Investigator: Sally H Ibbotson, MBChB, MD, University of Dundee

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 23, 2018
• Primary Completion (ACTUAL): October 10, 2019
• Study Completion (ACTUAL): October 10, 2019

Study Registration Dates

• First Submitted: November 3, 2016
• First Submitted That Met QC Criteria: December 1, 2016
• First Posted (ESTIMATE): December 6, 2016

Study Record Updates

• Last Update Posted (ACTUAL): March 9, 2021
• Last Update Submitted That Met QC Criteria: March 3, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Precancerous Conditions; Keratosis, Actinic; Keratosis; Dermatologic Agents; Antipruritics; Menthol
• Other Study ID Numbers: 2015PQ01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Findings of study will be shared through peer reviewed publications and presentations, although individual participant data not disclosed

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No